The purpose of the proposed research program is to gain further detailed information into the cellular mechanisms responsible for ion transport by epithelial tissues. These studies will involve (a) the determination of the current-voltage relation of the Na entry step in tight epithelia such as colon, urinary bladder, frog skin, etc., using a new developed and unique computer-driven voltage-clamp apparatus; (b) continued investigations of the intracellular Na, K and Cl thermodynamic activities of epithelial tissues determined using ion-selective microelectrodes in an effort to relate these activities to transcellular ion transport; (c) studies of the current-voltage relation of Na-coupled sugar and amino acid transport by small intestine in an effort to further define the kinetic characteristics of these carrier-mediated processes; and (d) to initiate studies of the transport and electrophysiologic properties of mono-layers of cultured renal and colonic epithelial cells in an effort to circumvent the problems that arise when one is dealing with the "natural" tissue characterized by an irregular geometry and heterogeneous cell types.